Personalized medicine is considered by many to be the wave of the future. A personalized medicine approach seeks to identify whether a given individual needs a given treatment or intervention prior to administering it, rather than relying on “standards” representing an average person in a group or population.
This approach is based on the well known fact that some individuals in a demographic population have naturally low or naturally high values which are not best measured against a statistical mean for the demographic population, but against that individual's own measured history.
For example, vaccines are a immunologic prophylactic whose frequency and dose is determined at the population level. Vaccines are approved for routine human use by regulatory agencies from different countries where the vaccines are to be applied, such as, for example, the U.S. the Food and Drug Administration (FDA). After approval, population-wide recommendations for use are made by various medical agencies, such as the Advisory Committee on Immunization Practices (ACIP), whose members represent experts in the vaccine field. The ACIP is a U.S. committee, to assist and advise the Secretary of Health and Human Services, as well as the Centers for Disease Control and Prevention (CDC), on how to best implement vaccination strategies to prevent disease. Written recommendations are developed with immunization schedules that are published and updated as needed for both pediatric and adult populations. From these recommendations, certain vaccines are mandated for school entry and government-sponsored programs.
Although such mandated schedules are the norm, the need for them varies across populations. They represent an a priori approach that does not take into account individual specifics. Immunity to disease wanes over time, but may be maintained at low levels or recalled, through immunologic memory, upon subsequent exposure to the corresponding infectious agent or cross-reactive antigens in the environment. For inactivated or subunit-based T cell-dependent vaccines, however, protective immunity may not last beyond 10 years.
For example, the protective responses to diphtheria, tetanus, and pertussis vaccines (DTaP, Td) have been shown to be absent after about 10 years, which is why Td (tetanus and diphtheria) boosters are recommended every 10 years. For T cell-independent vaccines, such as pneumococcal and meningococcal polysaccharides, there is no immunologic memory, and immunity may be gone in only 3 to 5 years. The result of these facts is that vaccinating everyone according to a standard protocol can often result in either under-vaccinating or over-vaccinating in various individual cases.
Result of Over-Vaccinating: Type III Hypersensitivity Reactions
Thus, while generalizations about the timing for boosters, whether at 3 or 5 or 10 years, represents one approach to the problem of maintaining long-term immunity, other problems can arise if the duration of immunity does not follow the expected pattern. For example, it is well known that Tetanus boosters for adults (such as, for example, those administered in emergency rooms to prevent tetanus after someone steps on a rusty nail), often lead to local adverse reactions at the injection site, particularly if the last booster was not too many years earlier. Because it may be difficult to determine when the last immunization was received for tetanus, health care providers tend to err on the side of caution by boosting.
While this general booster approach may readily prevent tetanus, the possibility of high levels of circulating antibodies may lead to an Arthus reaction, which is a local type III hypersensitivity reaction due to the development of immune complexes composed of IgG antibodies and the vaccine antigen. The immune complexes activate complement which binds to complement receptors on the mast cells to cause the release of granules and increased vascular permeability. This can ultimately lead to tissue damage. In an extreme case, a more generalized or systemic reaction can occur, where immune complexes are deposited in the kidneys and joints, leading to arthritis and glomerulonephritis. Subsequent cellular immune responses and tissue damage with respect to the glomerulus can lead to permanent loss of kidney function. The CDC has recently noted that certain vaccines produce increased rates of local or systemic reactions in certain recipients when administered too frequently, and that such reactions are thought to result from the formation of antigen-antibody complexes (Centers for Disease Control and Prevention, General Recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002; 51(No. RR-2):1-36).
A solution for the prevention of such a type III hypersensitivity problem resulting from over-vaccination would be to assess a person's immune status with respect to the offending antigen, and make an existential determination of when to optimally administer the vaccine booster. For example, concerning vaccinations for internationally adopted children of unknown immune status, the CDC states: “If avoiding unnecessary injections is desired, judicious use of serologic testing might be helpful in determining which immunizations are needed.” Regarding DTaP vaccinations specifically, the CDC also states: “If a revaccination approach is adopted and a severe local reaction occurs, serologic testing for specific IgG antibody to tetanus and diphtheria toxins can be measured before administering additional doses.” (see pages 20 and 21 of the CDC 2002 reference cited above.) In this way, serologic testing could be used to determine whether an antibody level is low enough to warrant further boosting of the immune system for a specific antigen, minimizing the risk of adverse reactions from over-vaccinations.
Result of Under-Vaccinating: Increased Susceptibility to Infection
Certain individuals may be genetically predisposed to infections as a result of a compromised immune system. For example, there are people that have been identified to be at greater risk of meningococcal disease due to late-stage complement deficiency, since complement usually mediates antibody-dependent killing of meningococci. Others have been shown to be susceptible to a variety of diseases (e.g., leprosy, salmonellosis, Pseudomonas aeruginosa infections, Yersinia infections, Listeria monocytogenes infections, streptococcal diseases, tuberculosis, Lyme disease, Chlamydia trachomatis infections, Helicobacter pylori infections, HIV disease, and various other viral infections) that appear to be correlated to a different HLA haplotype. Still others have been shown to have increased susceptibility to certain diseases (e.g., Haemophilus influenzae type B meningitis in Eskimos, Apaches, and Navajos) because their immune systems respond with a less effective antibody repertoire based on variable-region gene haplotypes. A solution to this susceptibility problem would be to screen people for the appropriate biologic or genetic markers and vaccinate accordingly. Vaccinations would help to enhance the compromised immune systems with higher levels of specific antibodies that could enable other immune mechanisms (e.g., opsonophagocytosis instead of complement-mediated lysis), overcome low antibody avidity with greater antibody numbers, or alter the relative balance of antibody repertoires. In addition, continuous serologic testing (e.g., annually) of the immune status would allow for optimum timing of vaccinations to counter the relentless waning of immunity over time while still avoiding the potential problems of over immunizing.
Determination of the immune status of individuals to, for example, vaccine-preventable diseases requires an assay system that can detect antibodies that may be present at very low levels, especially when natural or vaccine exposure may have been many years previously. In addition, such an assay system could be used more generally to assess an individual's immune competence at different stages of that individual's life, as well as to also measure the vaccine status of individuals with varying special needs and requirements (e.g., military personnel or travelers).
What is thus needed in the art is a system and method for measuring and processing immunologic information of individuals and populations through various points in time of their lives so as to better track each individual's immune status and make appropriate diagnostic, prophylactic and therapeutic recommendations.
What is further needed in the art is a supporting structure to conveniently store the results of such screenings for easy access and processing, for data mining purposes as well as for use in a variety of commercial, research and governmental applications where a knowledge of the immunological indicia of customers, subjects and citizens can create efficiencies and optimizations, as well as allow for the exploitation of commercial opportunities and improve the quality of life.